Induction of apoptosis in mouse brain capillary endothelial cells by cyclosporin A and tacrolimus

Satoko Kochi, Hitomi Takanaga, Hirotami Matsuo, Hisakazu Ohtani, Mikihiko Naito, Takashi Tsuruo, Yasufumi Sawada

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

Although cyclosporin A and tacrolimus are used clinically as potent immunosuppressants, there have been reports of neurotoxicity and encephalopathy. A possible mechanism is that these drugs damage the blood- brain barrier (BBB), inducing dysfunction and increased permeability, and are then able to enter the brain. We studied the cytotoxicity of cyclosporin A and tacrolimus, focused on apoptosis induction, using an immortalized cell line established from BALB/c mouse cerebral microvessel endothelial cells (MBEC4). We found that these two drugs induced cell shrinkage, chromatin condensation and DNA fragmentation, which are characteristics of apoptosis. Our data suggest that the induction of apoptosis on the brain capillary endothelial cells may be at least partly involved in the occurrence of immunosuppressant-induced encephalopathy.

Original languageEnglish
Pages (from-to)2255-2260
Number of pages6
JournalLife Sciences
Volume66
Issue number23
DOIs
Publication statusPublished - 2000 Apr 28

Keywords

  • Apoptosis
  • Blood-brain barrier
  • Cyclosporin A
  • Encephalopathy
  • Tacrolimus

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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